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Most voice hearers report childhood trauma. Many voice hearers report comorbid post-traumatic stress symptoms and that the content of their voices (auditory verbal hallucinations) is directly (voices repeat phrases spoken by perpetrators) or indirectly (voice content and trauma is thematically similar) related to their trauma. The factors that maintain trauma-related voices are unknown, and there is limited research in this area. This study aimed to identify potential maintaining factors of trauma-related voices by reviewing models of post-traumatic stress disorder (PTSD) and positive symptoms of psychosis.Models of PTSD and positive symptoms were reviewed to identify potential factors that are unique and common to both sets of symptoms.We reviewed 10 models of PTSD, 4 models of positive symptoms, and 2 trauma-informed models of voice hearing. One model provided a theoretical explanation of different types of trauma-related voices. Twenty-one factors were extracted from 16 theoretical models. No existing model incorporated all these factors.Existing PTSD and positive symptom models present a range of common and unique factors. There may be value in extending existing integrative models to include a broader range of potential factors that could explain different pathways to, and expressions of, trauma-related voices. A future research agenda is presented to investigate how such an extension could lead to more complete individualized case formulations and targeted treatments.

IMPORTANCE: Merkel cell carcinoma (MCC) often behaves aggressively; however, disease-recurrence data are not captured in national databases, and it is unclear what proportion of patients with MCC experience a recurrence (estimates vary from 27%-77%). Stage-specific recurrence data that includes time from diagnosis would provide more precise prognostic information and contribute to risk-appropriate clinical surveillance. OBJECTIVE: To estimate risk of stage-specific MCC recurrence and mortality over time since diagnosis. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 618 patients with MCC who were prospectively enrolled in a Seattle-based data repository between 2003 and 2019. Of these patients, 223 experienced a recurrence of MCC. Data analysis was performed July 2019 to November 2021. MAIN OUTCOMES AND MEASURES: Stage-specific recurrence and survival, as well as cumulative incidence and Kaplan-Meier analyses. RESULTS: Among the 618 patients included in the analysis (median [range] age, 69 [11-98] years; 227 [37%] female), the 5-year recurrence rate for MCC was 40%. Risk of recurrence in the first year was high (11% for patients with pathologic stage I, 33% for pathologic stage IIA/IIB, 30% for pathologic stage IIIA, 45% for pathologic stage IIIB, and 58% for pathologic stage IV), with 95% of recurrences occurring within the first 3 years. Median follow-up among living patients was 4.3 years. Beyond stage, 4 factors were associated with increased recurrence risk in univariable analyses: immunosuppression (hazard ratio [HR], 2.4; 95% CI, 1.7-3.3; P

Test anxiety, particularly cognitive test anxiety, is negatively associated with academic performance. Previous research has demonstrated that higher levels of perfectionistic concerns predict higher levels of cognitive test anxiety but has not explored potential mediators of this relationship. This study investigated whether repetitive negative thinking mediated the relationship between perfectionistic concerns and cognitive test anxiety in a non-clinical, academic sample.Participants were Australian university students (Mediation analysis yielded a total model accounting for 43.5% of variance in cognitive TA. Perfectionistic concerns significantly accounted for 10.6% of variance direction (Findings demonstrate that RNT significantly mediates the relationship between perfectionistic concerns and cognitive test anxiety in this sample. Importantly, these findings may direct future studies towards investigating the effectiveness of targeting repetitive negative thinking in interventions to mitigate levels of cognitive test anxiety.

We examine motives for ‘overbidding’ in contests between individuals using a “two-headed” approach to decision-making. In “two-headed” contests, subject pairs send suggested bids and messages to a partner. Content analysis of the messages provides insight into an individual’s bidding motives. In addition, we elicit measures of preferences, beliefs, and impulsiveness. We find that beliefs about others’ bids and messages that emphasize winning (i.e., utility of winning) are the most robust predictors of ‘overbidding’. Our results suggest that analyzing communication provides a rich window into an individual’s thought process when making decisions, and can complement insights from elicited values from common decision tasks (Replication materials, including data, do files, and software, are available at https://sites.google.com/view/david-bruner/research ).

Background Initial biopsies of cutaneous squamous cell carcinomas (cSCCs) may not reveal aggressive histologic features, which would otherwise inform appropriate surgical management and patient education. Objective To assess the incidence of, and risk factors for, histopathologic upgrading of cSCC during Mohs micrographic surgery (MMS). Methods This was a retrospective cohort study of invasive cSCCs treated with MMS between 2017 and 2019 at 1 academic institution. An “upgrade” was defined as a lesser degree of differentiation (poor or moderate) and/or bony or perineural invasion identified during MMS that was not reported in histopathologic evaluation of the initial biopsy. Results Of the 1558 tumors studied, 115 (7.4%) were upgraded during MMS. In multivariate logistic regression analysis, male sex, prior field treatment, location on the ear/lip, rapid growth of cSCC, and tumor diameter ≥2 cm were significant predictors of tumor upgrading. Upgraded tumors were more likely to require ≥3 MMS stages to clear, complicated closure (flap or graft), or outside (referral) repairs. Limitations Single-center study, retrospective, and inter-rater variability. Conclusions A significant proportion of cSCCs is histopathologically upgraded with more aggressive features during MMS. Routinely documented patient and tumor characteristics can predict tumor upgrading and assist clinicians in directing the management of potentially high-risk cSCC patients.

Maintaining organ homeostasis requires complex functional synergy between distinct cell types, a snapshot of which is glimpsed through the simultaneously broad and granular analysis provided by single-cell atlases. Knowledge of the transcriptional programs underpinning the complex and specialized functions of human kidney cell populations at homeostasis is limited by difficulty accessing healthy, fresh tissue. Here, we present a single-cell perspective of healthy human kidney from 19 living donors, with equal contribution from males and females, profiling the transcriptome of 27677 high-quality cells to map healthy kidney at high resolution. Our sex-balanced dataset revealed sex-based differences in gene expression within proximal tubular cells, specifically, increased anti-oxidant metallothionein genes in females and the predominance of aerobic metabolism-related genes in males. Functional differences in metabolism were confirmed between male and female proximal tubular cells, with male cells exhibiting higher oxidative phosphorylation and higher levels of energy precursor metabolites. Within the immune niche, we identified kidney-specific lymphocyte populations with unique transcriptional profiles indicative of kidney-adapted functions and validated findings by flow cytometry. We observed significant heterogeneity in resident myeloid populations and identified an MRC1+ LYVE1+ FOLR2+ C1QC+ population as the predominant myeloid population in healthy kidney. This study provides a detailed cellular map of healthy human kidney, revealing novel insights into the complexity of renal parenchymal cells and kidney-resident immune populations.

Background: Repetitive negative thinking is conceptualized to be a transdiagnostic process linked to the development and maintenance of psychopathology. Prior research distinguishes between disorder-specific exemplars (worry, rumination) and transdiagnostic measures of repetitive negative thinking with differences across disorders reported. However, establishing the measurement invariance of these measures is necessary to support meaningful comparisons across clinical groups. Method: Bayesian structural equation modelling was used to assess the approximate invariance of the Ruminative Response Scale, Penn State Worry Questionnaire, and the Repetitive Thinking Questionnaire across individuals with a principal diagnosis of either depressive disorder, social anxiety disorder, or generalized anxiety disorder. Results: All scales demonstrated approximate measurement invariance across the three disorder groups. The depressive disorder group reported a higher level of rumination than the generalized anxiety disorder group (Δµ = 0.25, 95% Credibility Interval [0.06, 0.45]), with no difference between the generalized anxiety disorder and social anxiety disorder groups. The depressive disorder and generalized anxiety disorder groups did not differ in their levels of trait repetitive negative thinking, but the social anxiety disorder group was markedly lower than the generalized anxiety disorder group (Δµ = −0.21 [−0.37, −0.05]). Similarly, levels of worry did not differ between the generalized anxiety disorder and depressive disorder group but were lower in the social anxiety disorder group than the generalized anxiety disorder group (Δµ = −0.23 [−0.41, −0.06]). Conclusions: The Ruminative Response Scale, Penn State Worry Questionnaire, and Repetitive Thinking Questionnaire are measuring trait repetitive negative thinking in a consistent manner across individuals with a principal diagnosis of depressive disorder, social anxiety disorder, or generalized anxiety disorder. This supports their use in transdiagnostic contexts and indicates that it is appropriate to directly compare the scores on these measures between diagnostic groups.

Abstract. Rumination is central to understanding the onset and maintenance of non-suicidal self-injury. Yet, no study has evaluated whether reported differences in rumination between people with and without a history of self-injury represent genuine group differences. The present study reports an investigation into the measurement invariance of three common measures of rumination in university students with and without a history of self-injury (total N = 1,519). Results revealed configural invariance for the Ruminative Responses Scale (RRS), the Ruminative Thought Style Questionnaire (RTSQ), and the Repetitive Thinking Questionnaire (RTQ). Additionally, the RTSQ and RTQ supported metric invariance, while the RRS supported partial metric invariance. Further, the RTQ demonstrated partial scalar invariance while the RTSQ demonstrated full scalar invariance. The current findings suggest that observed differences using the RTSQ and RTQ reflect genuine differences in rumination between people with and without a history of self-injury, while researchers using the RRS are advised to account for differential item functioning.

Objective: This study investigated research capacity and culture in people with lived experience of mental health challenges by developing a quantitative tool that measures capacity to engage in research. Method: A cross-sectional, correlational methodology was employed, which comprised of three phases: lived experience consultations for item development ( n = 15), item refinement ( n = 20) and tool piloting. Items were adapted from, and extended, an existing research capacity and culture tool for healthcare workers. People ( N = 112) with lived experience as mental health consumers, carers, peer workers and/or advocates aged 18–75 years took part in the tool piloting survey. Results: Overall, participants rated their individual research capacity and culture skills as moderate (mean = 5.41, standard deviation = 2.04). The most commonly reported barriers to research engagement related to lack of knowledge, familiarity or experience with the research process. The most commonly reported enablers were altruistic, such as using their experiences to improve services and help others. Research capacity and culture significantly correlated with current research activities ( rs = 0.25–0.41; ps 0.05), suggesting that building research capacity of people with lived experience requires them to be active members of research teams. Conclusion: The Lived Experience research capacity and culture tool developed in this study revealed that people with lived experience of mental health challenges are intrinsically motivated to engage in research to improve consumer outcomes. The tool may be useful to assess self, research team and organisational preparedness to conduct genuinely co-designed research, and to assess changes in lived experience research capacities and culture over time.

Kidney transplant recipients (KTRs) have a diminished response to SARS-CoV-2 vaccination compared with immunocompetent individuals. Deeper understanding of antibody responses in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron.We profiled antibody responses in KTRs pre- and at 1 and 3 mo post-third-dose SARS-CoV-2 mRNA-based vaccine. Binding antibody levels were determined by ELISA. Neutralization against wild type, Beta, Delta, and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike-pseudotyped lentivirus assay.Forty-four KTRs were analyzed at 1 and 3 mo (n = 26) post-third dose. At 1 mo, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 mo, but the proportion of KTRs with a robust antibody response was unchanged; 38.5% KTRs maintained Omicron-specific neutralization at 3 mo. No clinical variables were significantly associated with Omicron-neutralizing antibodies, but antireceptor binding domain titers appeared to identify those with Omicron-specific neutralizing capacity.Over 50% of KTRs lack Omicron-specific neutralization capacity 1 mo post-third mRNA-vaccine dose. Antibody levels of responders were well preserved at 3 mo. Anti receptor binding domain antibody titers may identify patients with a detectable Omicron-neutralizing antibody response.

Introduction The purpose of this study was to determine which components of sports medicine fellowships are most important to applicants when reviewing fellowship websites during the application process. Methods An anonymous survey was distributed to 492 fellowship applicants from the 2017-2018 and 2018-2019 cycles. The survey included questions about the importance of including components of fellow education, recruitment, and experience on program websites. The weighted average of responses determined each component’s rank, with 5 being “very important” and 1 being “not at all important.” Responses were analyzed by application cycle, current position, and sex using the Wilcoxon rank-sum test. Results Sixty-five applicants participated in the survey and completed the demographics section, resulting in a 13.2% response rate. According to participants, the most important components to include on fellowship websites were exposure to advanced operative sports medicine techniques (weighted average, 4.62), complexity of cases performed (4.52), and number of cases performed (4.50). Analysis demonstrated statistically significant differences in opinion between application cycles for flexibility for conducting a remote interview (P = .0074), jobs obtained by previous fellows (P = .019), national rank of department (P = .021), program’s geographic location (P = .026), protected academic time (P = .038), current positions for criteria for fellows’ performance evaluations (P = .028), program’s geographic location (P = .0097), and protected academic time (P = .0079). There were statistically significant differences in opinion between current positions regarding flexibility for conducting a remote interview (P = .0026), jobs obtained by previous fellows (P = .012), and national rank of department (P = .0013). Conclusions Orthopaedic sports medicine fellowship applicants believe that it is most important to include information about the volume and complexity of fellows’ cases and their day-to-day commitments on program websites. Clinical Relevance This information would enable applicants to identify programs that will support professional development and allow program directors to communicate expectations.

Repetitive thinking (RT) has been defined as prolonged, recurrent thought about oneself and one’s experiences. Recent studies have shown that various measures of RT load onto a common factor and predict symptoms of depression and anxiety. The relationship with mania symptoms, however, remains underexplored. The current study examined the common versus unique variance across a wide range of measures of RT, and the relationship between measures of RT and symptoms of anxiety, depression, and mania. Participants (N = 2088) were recruited from the United States, Australia, and the Netherlands. Participants were administered various measures of RT and measures of depression, anxiety, and mania symptoms. Single and bifactor models were examined. A bifactor model—accounting for both a common factor and unique variance within each measure—explained the data well, indicating that disorder specific measures of RT can be combined to measure a higher order RT factor. The common factor also significantly correlated with symptoms of depression, anxiety, and mania. Our findings indicate that combining measures of RT can help public health researchers predict not only depression and anxiety, but also symptoms of mania.

Background LGBQ+ people (Lesbian, Gay, Bisexual, Queer) are at-risk of discrimination and developing mental health issues within general populations. Limited research has assessed their mental health in emergency services occupations, a population which are known to experience poorer mental health. The current study explores the extent to which sexual orientation is associated with higher rates of mental health issues among emergency personnel. Methods A stratified random sample of employees from twenty-nine police (N = 8,088), ambulance (N = 3,473), and fire and rescue (N = 2,975) agencies from around Australia participated in a cross-sectional mental health survey (N = 14,536, male = 64.2%, 42.7% over 45 years of age, heterosexual = 92.7%). Results Employees with a bisexual/pansexual orientation or those who were not sure about their sexual orientation were significantly more likely to report suicidal thoughts, suicide plans, psychological distress, and illicit drug use when compared with heterosexual employees. LGBQ+ employees reported significantly higher rates of lifetime suicide plans and attempts. Specifically, LGBQ+ fire and rescue personnel were roughly six times more likely to report lifetime suicide attempts, and approximately five times more likely to use illicit drugs weekly than their heterosexual colleagues in the fire and rescue sector. Female LGBQ+ personnel were significantly less likely to consume illicit drugs weekly and monthly than male LGBQ+ personnel. Conclusions Emergency services personnel are already at-risk of developing pervasive mental health difficulties. It is important that organisations foster positive working environments, particularly for LGBQ+ people who may be more marginalized within organisations.

Emergency services personnel have an elevated risk of developing mental health conditions. Most research in this area is cross-sectional, which precludes inferences about temporal and potentially causal relationships between risk and protective factors and mental health outcomes. The current study systematically reviewed prospective studies of risk and protective factors for mental health outcomes in civilian emergency services personnel (firefighters, paramedics, police) assessed at pre-operational and operational stages. Out of 66 eligible prospective studies identified, several core groups of risk and protective factors emerged: (1) cognitive abilities; (2) coping tendencies; (3) personality factors; (4) peritraumatic reactions and post-trauma symptoms; (5) workplace factors; (6) interpersonal factors; (7) events away from work. Although there was insufficient evidence for many associations, social support was consistently found to protect against the development of mental health conditions, and peritraumatic dissociation, prior mental health issues, and prior trauma exposure were risk factors for future mental health conditions. Among operational studies, neuroticism was significantly associated with future PTSD symptoms, burnout, and general poor mental health, and avoidance and intrusion symptoms of PTSD were associated with future PTSD and depression symptoms. The current review results provide important targets for future research and interventions designed to improve the mental health of emergency services personnel.

Background: Kidney transplant recipients (KTR) have a diminished response to SARS-CoV-2 vaccination in comparison to immunocompetent individuals. Deeper understanding of the antibody response in KTRs following third-dose vaccination would enable identification of those who remain unprotected against Omicron and require additional treatment strategies. Methods: We profiled antibody responses in KTRs pre- and at one and three months post-third-dose SARS-CoV2 mRNA-based vaccine. Anti-spike and anti-RBD IgG levels were determined by ELISA. Neutralization against wild-type, Beta, Delta and Omicron (BA.1) variants was determined using a SARS-CoV-2 spike pseudotyped lentivirus assay. Results: 44 KTRs were analysed at 1 and 3 months (n=26) post-third-dose. At one month, the proportion of participants with a robust antibody response had increased significantly from baseline, but Omicron-specific neutralizing antibodies were detected in just 45% of KTRs. Median binding antibody levels declined at 3 months, but the proportion of KTRs with a robust antibody response was unchanged. 38.5% KTRs maintained Omicron-specific neutralization at 3 months. No clinical variables were significantly associated with detectable Omicron neutralizing antibodies, but anti-RBD titres appeared to identify those with Omicron-specific neutralizing capacity. Conclusion: Over 50% of KTRs lack an Omicron-specific neutralization response 1 month following a third mRNA-vaccine dose. Among responders, binding and neutralizing antibody responses were well preserved at 3 months. Anti-RBD antibody titres may be a useful identifier of patients with detectable Omicron neutralizing antibody response. Trial registration: Clinical Trials Ontario: ID 3604

This third edition provides a thorough real-world exploration of the scientist-practitioner model, enabling clinical psychology trainees to develop the core competencies required in an increasingly interdisciplinary healthcare environment. The book has been comprehensively revised to reflect shifts towards transdiagnostic practice, co-design principles, and personalized medicine, and features new chapters on low intensity psychological interventions and private practice. Fully updated for the DSM-5 and ICD-11, provides readers with a contemporary account of diagnoses. It covers practical skills such as interviewing, diagnosis, assessment, case formulation, treatment, case management, and process issues with emphasis on the question 'how would a scientist-practitioner think and act?' The book equips trainees to deliver the accountable, efficient, and effective client-centred service demanded of professionals in the modern integrated care setting by demonstrating how an evidence-base can influence every decision of a clinical psychologist. Essential reading for all those enrolled in, or contemplating, postgraduate studies in clinical psychology.

BACKGROUND The Bivalent Fear of Evaluation Model proposes that the fears of positive and negative evaluation each uniquely contribute to social anxiety severity. However, the debate continues as to whether these are distinct constructs, and, if so, the degree of influence each has on social anxiety severity. This study used a longitudinal evaluation of these relationships in a clinical sample to identify whether the two fears differentially change over time and differentially relate to social anxiety severity. METHODS Individuals with a social anxiety disorder (N = 105) completed measures of fears of negative and positive evaluation weekly, and social interaction anxiety monthly, for 12 weeks. Temporal relationships were assessed using residual dynamic structural equation modeling. RESULTS Fears of positive and negative evaluation both predicted the future status of the other (ϕ = 0.18, 95% credibility interval [0.10-0.28] and ϕ = 0.22 [0.12-0.35], respectively). Fear of negative evaluation (ϕ = 0.16 [0.05-0.28]) but not positive evaluation (ϕ

BackgroundCognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.MethodsA randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.ResultsIntention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).ConclusionsGroup IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.

BACKGROUND: Antibody-mediated rejection (AMR) accounts for >50% of kidney allograft loss. Donor-specific antibodies (DSA) against HLA and non-HLA antigens in the glomeruli and the tubulointerstitium cause AMR while inflammatory cytokines such as TNFα trigger graft injury. The mechanisms governing cell-specific injury in AMR remain unclear. METHODS: Unbiased proteomic analysis of laser-captured and microdissected glomeruli and tubulointerstitium was performed on 30 for-cause kidney biopsy specimens with early AMR, acute cellular rejection (ACR), or acute tubular necrosis (ATN). RESULTS: A total of 107 of 2026 glomerular and 112 of 2399 tubulointerstitial proteins was significantly differentially expressed in AMR versus ACR; 112 of 2026 glomerular and 181 of 2399 tubulointerstitial proteins were significantly dysregulated in AMR versus ATN (P

PURPOSE. To evaluate the cost-effectiveness of axillary observation versus sentinel lymph node biopsy (SLNB) after negative axillary ultrasound (AUS). In patients with clinical T1-T2 N0 breast cancer and negative AUS, SLNB is the current standard of care for axillary staging. However, SLNB is costly, invasive, decreasing in importance for medical decision-making, and is not considered therapeutic. Observation alone is currently being evaluated in randomized clinical trials, and is thought to be noninferior to SLNB. METHODS. We performed cost-effectiveness analyses of observation versus SLNB after negative AUS in post-menopausal women with clinical T1-T2 N0, HR(+)/HER2(−) breast cancer. Costs at the 2016 price level were evaluated from a third-party commercial payer perspective using the MarketScan® Database. We compared cost, quality-adjusted life years (QALYs), and net monetary benefit (NMB). Multiple sensitivity analyses varying baseline probabilities, costs, utilities, and willingness-to-pay thresholds were performed. RESULTS. Observation was superior to SLNB for patients with N0 and N1 disease, and for the entire patient population (NMB in US$: $655,659 for observation versus $641,778 for SLNB for the entire patient population). In the N0 and N1 groups, observation incurred lower cost and was associated with greater QALYs. SLNB was superior for patients with >3 positive lymph nodes, representing approximately 5% of the population. Sensitivity analyses consistently demonstrated that observation is the optimal strategy for AUS-negative patients. CONCLUSION. Considering both cost and effectiveness, observation is superior to SLNB in post-menopausal women with cT1-T2 N0, HR(+)/HER2− breast cancer and negative AUS.

Fibrosis is a central pathway that drives progression of multiple chronic diseases, yet few safe and effective clinical antifibrotic therapies exist. In most fibrotic disorders, transforming growth factor–β (TGF-β)–driven scarring is an important pathologic feature and a key contributor to disease progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two closely related transcription cofactors that are important for coordinating fibrogenesis after organ injury, but how they are activated in response to tissue injury has, so far, remained unclear. Here, we describe NUAK family kinase 1 (NUAK1) as a TGF-β–inducible profibrotic kinase that is up-regulated in multiple fibrotic organs in mice and humans. Mechanistically, we show that TGF-β induces a rapid increase in NUAK1 in fibroblasts. NUAK1, in turn, can promote profibrotic YAP and TGF-β/SMAD signaling, ultimately leading to organ scarring. Moreover, activated YAP and TAZ can induce further NUAK1 expression, creating a profibrotic positive feedback loop that enables persistent fibrosis. Using mouse models of kidney, lung, and liver fibrosis, we demonstrate that this fibrogenic signaling loop can be interrupted via fibroblast-specific loss of NUAK1 expression, leading to marked attenuation of fibrosis. Pharmacologic NUAK1 inhibition also reduced scarring, either when initiated immediately after injury or when initiated after fibrosis was already established. Together, our data suggest that NUAK1 plays a critical, previously unrecognized role in fibrogenesis and represents an attractive target for strategies that aim to slow fibrotic disease progression.